Pharmacokinetics of topical and oral antifungals

By principle both topical and systemic antifungals are available for oral candidosis. As therapeutic results have not yet reached an optimum these modalities deserve further consideration. This especially applies to bioavailability. As candidosis in general very often is a disease confined to other tissues than blood especially to cutaneous and mucosal surfaces, it is helpful to determine the drug level found at these sites. Both total and free drug levels should be looked at. The skin blistering techniques make this possible. In vitro simulation of the level profiles of various antifungals including in particular ketoconazole found in the skin can be simulated in vitro using Grasso's model. If this is done only a very limited candidacidal effect is to be seen. Taking this fact into account as well as a limited clinical efficacy of conventional treatment protocols it looks rewarding to use conventional antifungal drugs such as ketoconazole at comparatively high doses.